Clinical Review

Decision Making in Venous Thromboembolism

Journal of Clinical Outcomes Management. 2015 May;22(5)

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These TSOACs show promise in treatment and prevention of VTE but should be used in patients who meet appropriate criteria for renal function, age, and bleeding risk, as there are currently no available antidotes to reverse their effects. If significant bleeding occurs and cannot be controlled by usual maneuvers such as mechanical compression or surgical intervention, there is little data to guide the use of pharmacologic interventions. Plasma dabigatran levels can be reduced through the use of hemodialysis [146].Antibodies capable of neutralizing dabigatran have been developed, and one specific antibody, idarucizumab, was well-tolerated and showed immediate and complete reversal of dabigatran in subjects of different age and renal function [147,148].Andexanet, a modified recombinant derivative of factor Xa with no catalytic activty, acts as a “decoy receptor” with higher affinity to factor Xa inhibitors than natural factor Xa. Phase II studies in healthy volunteers demonstrated that andexanet immediately reversed the anticoagulation activity of apixaban, rivaroxaban, enoxaparin, and most recently edoxaban without thrombotic consequences [149].Two randomized, double-blind, placebo-controlled phase III studies (ANNEXA-A, looking at the reversal of apixaban, and ANNEXA-R, looking at reversal of rivaroxaban) are underway, and preliminary results show that a single intravenous bolus of andexanet demonstrated almost complete reversal [150].Finally, aripazine (PER977), a synthetic small molecule that binds to heparins as well as all TSOACs, was shown in a phase II trial to decrease blood clotting time to within 10% above baseline value in 10 minutes or less with an effect lasting for 24 hours [151].

Some have advocated for use of prothrombin complex concentrate (PCC) or recombinant factor VIIa for reversal of TSOAC-associated bleeding. Rivaroxaban was demonstrated to be partially reversible by PCC, whereas this approach was not as successful for dabigatran in healthy volunteers [152].In vitro evidence, however, showed that PCC did not significantly change aPTT [153].At present, the use of nonspecific hemostatic agents (including recombinant factor VIIa, 4-factor prothrombin complex concentrate, and activated prothrombin complex concentrates) is suggested for reversal of TSOACs in patients who present with life-threatening bleeding [154,155].

Conclusion

Patients with VTE present with a wide range of findings and factors that impact management. Decision making in VTE management is a fluid process that should be re-evaluated as new data emerge and individual circumstances change. There is more focus on VTE prevention and treatment today than there was even a decade ago. Diagnostic algorithms, identification of new risk factors, refinement in understanding of the pathogenesis of thrombosis, and identification of new anticoagulants with more favorable risk-benefit profiles will all ultimately contribute to improved patient care.

Corresponding author: Jean M. Connors, MD, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02215.